1. Field of Invention
This invention relates to certain novel dibenzopyrans and, more particularly, to 9-hydroxyhexahydrodibenzo[b,d]pyrans, 1-substituted-9-hydroxyhexahydrodibenzo[b,d]pyrans wherein the substituent is hydrogenn, methyl, hydroxymethyl, formyl, carboxy, carbamyl, amino, mono- or dialkylamino, alkanoylamino, phenalkylsulfonamido or alkylsulfonamido, and the corresponding 9-ketones having at the 3-position an alkyl, aralkyl or pyridylalkyl, in each of which an oxygen atom can be present at some point in the alkyl moiety, or phenoxy or pyridyloxy, the use of such compounds as CNS agents, especially as tranquilizers and analgesics in mammals, including man, intermediates therefor, and processes for preparation of such compounds.
2. Description of the Prior Art
Despite the current availability of a number of analgesic agents, the search for new and improved agents continues, thus pointing to the lack of an agent useful for the control of broad levels of pain and accompanied by a minimum of side-effects. Aspirin, the most commonly used agent, is of no practical value for the control of severe pain and is known to exhibit various undesirable side-effects. Other, more potent analgesic agents such as d-propoxyphene, codeine and morphine, possess addictive liability. The need for improved and potent analgesic agents is, therefore, evident.
The preparation and analgesic properties of tetrahydro- and hexahydro-1-amino-3-alkyl-6H-dibenzo[b,d]pyrans having at the 9-position a hydrogen or a methyl group are described in U.S. Pat. No. 3,886,184, issued May 27, 1975.
Mechoulam et al., Chem. Revs., 76, 75-112 (1976) discuss several derivatives of .DELTA..sup.1 -and .DELTA..sup.6 -tetrahydrocannabinols which have at the 9-position a hydrogen, methyl, hydroxymethyl, formyl or carboxyl group. No references to the preparation and properties of saturated A-ring cannabinol-like compounds having such substituents at the 1-position are known.
U.S. Pat. No. 3,901,926, issued Aug. 26, 1975, describes 1-hydroxy-3-aralkyl-6,6-di(lower alkyl)-hexahydrodibenzo[b,d]pyrans having hydrogen or methyl at the 9-position which are useful as analgesic agents. U.S. Pat. Nos. 3,507,885 and 3,636,058, issued Apr. 21, 1970 and Jan. 18, 1972, respectively, describe various 1-hydroxy-3-alkyl-6H-dibenzo[b,d]pyrans having at the 9-position substituents such as oxo, hydrocarbyl and hydrocarbylidene useful as psychotropic and analgesic agents, and intermediates therefor.
Mechoulam et al., pages 129-130 in "Marijuana, Chemistry, Pharmacology and Clinical Effects", Academic Press, New York, N. Y. 1973, summarize structure-activity relationships in the cannabinoids. With respect to the 1-position, the implication is that an aromatic hydroxyl group is essential for activity. Blocking of the hydroxyl group at the 1-position as an ether group inactivates the molecule. Additionally, it is noted that introduction of a hydroxyl group on the methyl group at the 9-position retains activity. No studies appear to have been made as to the effect of substitution of groups other than hydroxyl, methyl ether or acetoxy at the 1-position.